Myotilinopathy: refining the clinical and myopathological phenotype

Brain. 2005 Oct;128(Pt 10):2315-26. doi: 10.1093/brain/awh576. Epub 2005 Jun 9.


Mutations in myotilin gene (MYOT) have been associated with variable syndromes including limb girdle muscular dystrophy type 1A (LGMD1A) and a subgroup of myofibrillar myopathy (MFM/MYOT). We studied six Spanish patients from three unrelated kindreds and seven patients without family history. Three previously reported and two novel disease-associated MYOT mutations were identified in this group of patients. The disease is characterized by the onset at the age of 42-77 years with muscle weakness initially in distal or proximal leg muscles, eventually spreading to other muscle groups of the lower and upper extremities. Associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy are present in a fraction of patients. Myopathological features of focal myofibrillar destruction resulting in intracytoplasmic deposits, strongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally located non-rimmed vacuoles and streaming Z-lines, were observed in each patient studied. The Spanish cohort, the largest group of patients studied so far, shares phenotypic features with both LGMD1A and MFM/MYOT variants thus establishing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Arm
  • Connectin
  • Cytoskeletal Proteins / genetics*
  • Family Health
  • Female
  • Humans
  • Leg
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Muscle Proteins / genetics*
  • Muscle Weakness / genetics
  • Muscle Weakness / pathology
  • Muscle, Skeletal / pathology
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology
  • Muscular Dystrophies, Limb-Girdle / genetics
  • Mutation, Missense / genetics
  • Myofibrils / genetics*
  • Myofibrils / pathology
  • Pedigree
  • Phenotype
  • Tomography, X-Ray Computed / methods


  • Connectin
  • Cytoskeletal Proteins
  • MYOT protein, human
  • Microfilament Proteins
  • Muscle Proteins